Precision Medicine DTP - Novel computational modelling for personalised treatment of osteoarthritis

Additional supervisor: Prof Hamish Simpson

Background

Osteoarthritis (OA) is a condition that causes joints to become painful and stiff. Nearly one third of population aged above 45 are affected by OA in the UK. In spite of considerable ongoing research, pathways to OA are not well understood. OA has been generally seen to be caused by the wearing down of protective cartilage. However, there continues to be a debate about whether OA starts in the bone, with increased sclerosis and stiffness and that this results in cartilage deterioration or whether OA starts in the articular cartilage. The current proposal is that OA needs to be viewed as end stage joint failure, with different components of the joint all contributing to the failure.

Both bone and the cartilage are inhomogeneos, anisotropic and time-dependent materials (Xie et al., 2017; Klika et al., 2016). Consequently their response is strongly dependent on the type, rate, magnitude and frequency of loading. In the computational analysis of bone- cartilage systems the time-dependent behavior of bone has not been previously taken into account. The cartilage is highly complex inhomogeneous material with a distinct location dependent biochemical and morphological variations (Mow et al., 2004). The mechanical properties of cartilage vary along the depth (Dabiri and Li, 2013) as well as along the articular surface (Mow et al., 2004). The depth dependent material behaviour has been investigated previously (Dabiri and Li, 2013), but the site-dependency along the articulating surface has not been well established. We hypothesise that the biomechanical physiological loading patterns affect the material response along articular surface as well as along the depth, in both bone and the cartilage.

Aims

The primary aim of the study is to establish the inter-relationship of initial cartilage quality, subchondral bone stiffness and loading scenarios (due to different physiological activies which result in loads with varying magnitudes, frequencies and strain rates) by using computational models to optimise osteoarthritis treatment.

Outline: The research will be conducted by using data from mechanical testing and imaging of testing clinical samples in conjunction with available physiological loading data. Novel computational simulations using the finite element method will be employed. A range of cartilage properties will be considered; variation of properties from normal to cartilage weakened by infection or inflammation will be considered. Similarly the material properties of the subchondral bone will be varied to represent subchondral sclerosis. The findings of this project will enable the interplay of bone and cartilage properties and loading to be considered in different patients. This will indicate the leading mechanism of joint failure in different patients, which will allow us to personalize the treatment inline with the principles of precision medicine.

Training outcomes

By the end of the training the trainee should be able to:

- Present and critique the state-of-art with respect to the initiation and development OA.
- Develop complex geometry of joints for finite element analysis from 3D scan data.
- Conduct micro-CT scans of explants.
- Describethemathematicalconstitutivemodelsofcomponentsinvolvedinmodelling.
- Develop algorithms and code constitutive models for implementation in finite element packages.
- Develop algorithms that incorporate change in macroscale properties of cartilage due to variation in micro-environment of cells.-
- Describe loadings experienced by the knee due to different physiological activities.
- Develop protocols and undertake mechanical tests on explants and simulate the results using cutting edge computational approaches.
- Learn to generate, curate and analyse large datasets.
- Master techniques for data analysis obtained from computational modelling.
- Work in a team and be become self reliant for acquiring resources required for research.
- Present research in international conferences and write journal papers.

This MRC programme is joint between the Universities of Edinburgh and Glasgow. You will be registered at the host institution of the primary supervisor detailed in your project selection.

All applications should be made via the University of Edinburgh, irrespective of project location. For those applying to a University of Glasgow project, your application along with any supporting documents will be shared with University of Glasgow.

http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=919

Please note, you must apply to one of the projects and you must contact the primary supervisor prior to making your application. Additional information on the application process is available from the link above.

For more information about Precision Medicine visit:
http://www.ed.ac.uk/usher/precision-medicine